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7-2015

Current Management of Heart Failure: When to Refer to Heart Current Management of Heart Failure: When to Refer to Heart

Failure Specialist and When Hospice is the Best Option. Failure Specialist and When Hospice is the Best Option.

Behnam Bozorgnia Einstein Medical Center

Paul J. Mather Thomas Jefferson University

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Bozorgnia, Behnam and Mather, Paul J., "Current Management of Heart Failure: When to Refer to

Heart Failure Specialist and When Hospice is the Best Option." (2015). Division of Cardiology

Faculty Papers. Paper 59.

https://jdc.jefferson.edu/cardiologyfp/59

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1

Heart Failure (HF) is a common syndrome caused by different pathologies of the

cardiovascular system that result in impairment of the ventricles to fill or eject blood.

Heart failure is one of the most common causes of hospitalization in United States with

a very high cost to the healthcare system. There are 880,000 new heart failure

diagnoses per year in the United States and 5 million cases currently identified in the

US. (1-2). In this chapter we will focus on the etiologies of the left ventricle (LV)

dysfunction, presentation and, the acute and chronic management of heart failure.

Etiologies of Heart failure

There is a broad spectrum of pathologies that cause LV dysfunction. The etiologies of

systolic and diastolic dysfunction include of coronary artery disease, hypertension,

valvular heart disease, to more rare etiologies such as infiltrative disorders and parasitic

infections. Table 1. lists the most common of the etiologies of HF encountered by

clinicians

Table 1

Etiologies of Heart failure

Myocardial disease

1. Coronary artery disease

2. Hypertension

3. Cardiomyopathy

a. Familial

i. Hypertrophic

ii. Dilated

iii. Arrhythmogenic right ventricular cardiomyopathy

iv. Restrictive

v. Left ventricular non-compaction

b. Acquired

i. Myocarditis

Infective

• Bacterial

• Spirochaetal

• Fungal

• Protozoal

• Parasitic

• Rickettsial

• Viral

Immune-mediated

• Tetanus toxoid, vaccines, serum sickness

• Drugs

• Lymphocytic/giant cell myocarditis

• Sarcoidosis

• Autoimmune

• Eosinophilic (Churg-Strauss)

2

Toxic

• Drugs (Chemotherapy, cocaine)

• Alcohol

• Heavy metals (copper, iron, lead)

ii. Endocrine/nutritional

• Phaeochromocytoma

• Vitamin deficiency (e.g. thiamine)

• Selenium deficiency

• Hypophosphataemia

• Hypocalcaemia

iii. Pregnancy

iv. Infiltration

• Amyloid

• Malignancy

Valvular Heart Disease

• Mitral

• Aortic

• Tricuspid

• Pulmonary

Pericardial Disease

• Constrictive pericarditis

• Pericardial effusion

Congenital Heart Disease

Arrhythmia

• Tachycardia (atrial, Ventricular)

• Bradyarrhythmia (Sinus node dysfunction, Atrioventricular block)

High Output States

• Anemia

• Sepsis

• Thyrotoxicosis

• Paget’s disease

• Arteriovenous fistula

Volume Overload

• Renal failure

• Iatrogenic (post-operative fluid infusion)

Table 1. Etiologies of Heart Failure. Adapted from European Society of Cardiology Guidelines, European Heart

Journal, 2012

Acute Heart Failure

Common presenting symptoms of HF can include mild shortness of breath, peripheral

edema and fatigue, to more severe symptoms such as hypotension, syncope, shock

and respiratory failure. A thorough history and physical exam is critical in diagnosis and

treatment of patients with HF. The presence of risk factors for developing HF such as

3

coronary artery disease, hypertension, and diabetes and the presence of substance

abuse or recent viral syndrome can provide clues for the etiology of HF. Exposure to

chemotherapeutic agents, endocrine abnormalities, recent pregnancy, family history of

HF or transplant are all subjects that should be addressed during the initial interview of

the patient with HF. A comprehensive history will narrow down the extensive list of

etiologies and allows the clinician to provide a more focused and tailored therapy.

Physical Exam

Vital Signs: Evaluation of the HF patient starts with the vital signs. An elevated

temperature can be present in myocarditis, or acute valvular lesions in infective

endocarditis. Heart rate and regularity is also an imperative parameter in evaluating a

patient with HF. Presence of tachycardia is an important and often ominous finding in

acutely decompensated HF. Blood pressure can vary significantly depending on the

stage and severity of the disease. HF patient can present to Emergency Room with very

high systolic and diastolic pressures and acute pulmonary edema. A narrow pulse

pressure (less than 25%) is a sign of low cardiac output and severely decompensated

HF patient.

The patient’s state of mind and clarity can be determined during the interview. Low

cardiac output can manifest itself as a confused and difficult to arouse patient.

Evaluation of the jugular venous pressure (JVP) is probably the most important and

challenging part of the exam of the HF patient. JVP will determine the volume status of

the patient which will guide the HF therapy. JVP can also differentiate intravascular

volume overload from extravascular edema present in other conditions. Presence of

rales in an acute setting is common, although the absence of rales does not rule out HF

especially in a patient with chronic HF. The cardiac exam includes the regularity of the

rhythm, and the presence of murmurs and gallops. A displaced point of maximal

impulse (PMI) is indicative of an enlarged heart. The abdominal exam includes the size

of the liver and presence of edema. Ascites, sacral, scrotal, or lower extremity edema

can be present in a volume overloaded patient with manifestations of right-sided heart

failure. Cool extremities and low pulse volume can be another sign of the hypo-

perfused patient with low cardiac output. Palpation of the peripheral pulses can also be

helpful in assessing cardiac in assessing cardiac performance and stroke volume. A full

and round pulse as compared to a short and pointed pulse can be the difference in a

compensated HF patient or a sign of low cardiac output respectively.

Diagnostic Tests

Chest X-ray: CXR findings can be specific but not sensitive for diagnosing HF.

Classically, presence of Kerley B lines, Peribronchial cuffing, pleural effusions, and

cephalization of the pulmonary vasculature can be present in HF patients.

4

Electrocardiogram: ECG determines the presence of any arrhythmias that are common

in HF patients. Presence of Q waves, or ischemic changes such as ST elevation or

depressions vs. left ventricular hypertrophy or low voltage may guide the clinician

towards the correct etiology of HF.

Laboratory Data: Patients with acute HF can present with low sodium levels.

BUN/Creatinine can also be abnormal depending of the degree of decompensation and

hypoperfusion. B-type natriuretic peptide (BNP), or N-terminal pro-B-type natriuretic

peptide (NT-proBNP) measurements are useful in an acutely decompensated patient

(4-5). Although the absolute value of each lab value can be variable, both BNP and NT-

proBNP can be useful in distinguishing HF from other common conditions when clinical

picture is not clear (Class I indication). Of note, BNP levels can be falsely low in

morbidly obese patients.

Other lab values to consider are as following:

• Troponin

• Thyroid stimulating hormone (TSH)

• Iron studies

• HIV

• Liver function test (LFT)

Troponin levels can be elevated in both ischemic and non ischemic HF patients.

Persistent elevation of troponin levels does have a poor prognostic value in HF patients

(6). Liver function can also be a marker of the level of congestion and chronicity of HF.

In appropriate patients, HIV and Iron level are helpful to further narrow down the

etiology of HF.

Acute Heart failure Therapy

Once the underlying cause of HF is identified, the HF therapy can be tailored to the

individual patient. When evaluating a patient with acute HF, it is important to assess the

level of congestion, i.e. “wet” vs. “dry” and also the level of perfusion, “warm” vs. “cold”.

The level of congestion and perfusion of the HF patient will guide the initial therapy.

Figure 1. provides a quick assessment of the hemodynamic profile of the HF patient.

5

A quick assessment of the hemodynamic profile is critical prior to initiation therapy since

the spectrum of therapy can be variable and wide. Patient profile A (warm and dry) can

be managed as outpatient, while patient profile C (cold/wet) will need inotrope or

mechanical circulatory support.

Diuretics

Diuretic therapy is initiated in the acute setting to alleviate symptoms. Parenteral diuretic

therapy should be initiated in an acute setting in a congested patient with adequate

perfusion. The diuretic dose should be adjusted frequently until adequate response is

obtained. Most commonly used loop diuretic is furosamide. Other diuretics such as

bumetanide or torsemide are also utilized for their increased bioavailability in the oral

form.

The diuretic effect of loop diuretics can be enhanced by addition of thiazide diuretics

such as metolazone or spironolactone in a diuretic resistance patient (8). Renal

function and electrolytes need to be monitored closely during aggressive parenteral

diuresis.

6

When compared IV bolus vs. continuous infusion of loop diuretics, the data has not

shown significant difference between the two strategies (9). The clinician however can

choose either method if the patient is refractory to the initial therapy.

Parenteral Vasodilators

Parenteral vasodilators are used as adjuvant therapy to diuretics to relieve congestion

and dyspnea in acute HF patient without hypotension. This class of medications

increase systemic perfusion, including the renal system and therefore enhance the

diuretic effect of loop diuretics.

Intravenous nitroglycerin can relieve congestion primarily through venodilation. This

medication is mainly used in hypertensive patients with pulmonary edema. Intravenous

nitroglycerin can also relieve symptoms of angina in patients with significant coronary

disease. This medication is usually effective up to 24 hours. Patients can develop

tachyphylaxis or resistance to nitroglycerin during this time (10).

Sodium Nitroprusside is another potent vasodilator used to treat acute HF. This

medication relieves congestion by dilating the venous and arterial beds and reducing

the systemic vascular resistance. Arterial line hemodynamic monitoring is usually

needed during therapy as Nitroprusside can cause precipitous hypotension. Rare

thiocyanate toxicity can occur with prolonged use particularly in patients with renal

impairment (11).

Nesiritide can also be used to relieve symptoms of dyspnea and enhance diuresis in

acute HF. As other vasodilators mentioned above, hypotension is a side effect during

therapy. Brain natriuretic peptide (BNP) levels are not reliable during administration of

Nesiritide. It is also important to note that the above vasodilators have not shown any

mortality benefit for HF patient and are only utilized in the acute setting for symptomatic

relief (12).

Beta Blockers

Beta Blockers (BB) are important class of drugs used in treatment of HF (13). In an

acute presentation of HF however their use requires some clinical judgment and

finesse. BB can be initiated at low dose, or continued if the patient is already on BB

therapy as outpatient, in a well perfused patient. Titration of this class of drugs however

should be avoided during the acute phase of HF. BB dose should be reduced or

7

stopped in more severe presentation of HF. It is imperative however that the patient be

initiated on BB therapy prior to discharge to ensure use as transitions of care occur.

Sinus tachycardia is often present in acute HF presentation. One should refrain from

titrating the BB dose in order to suppress sinus tachycardia in HF. In an acutely

decompensated HF, sinus tachycardia is an appropriate and crucial physiological

response to a low cardiac output state. Sinus tachycardia is usually resolved as the

hemodynamic profile of the HF patient improves.

The literature on HF and BB is extensive. There are however mixed results with certain

BB medications. For that reason, current recommendations encourage clinicians to use

1 of the 3 BBs that have showed benefit in clinical trials; Bisoprolol, Metoprolol

Succinate, or Carvedilol. Table 2. Lists the target doses of the BBs in treatment of HF

(13-16).

Angiotensin-Converting Enzyme Inhibitors

ACE inhibitors are the cornerstone of HF therapy (17-18). The vasodilation effects of

ACE inhibitors are key in improving hemodynamics of HF in both acute and chronic

state. Unlike BBs, ACE inhibitors do exhibit class effect. In acute HF patient without

shock or significant renal dysfunction, ACE inhibitors should be initiated at low dose and

titrated to the maximum tolerated dose. Short acting ACE inhibitors such as Captopril

can be initiated in the acute setting if there is concern about hypotensive response. If

tolerated, the short acting Captopril should be switched to a comparable dose of a long

acting ACE inhibitor such as Lisinopril or Enalapril. Table 2. Lists the target doses of the

ACE inhibitors in treatment of HF.

Angiotensin-receptor Blockers (ARBs)

ARBs are also vasodilators that can be utilized instead of ACE inhibitors in patients with

acute HF (19-21). ARBs are used when patients exhibit ACE inhibitor intolerance such

as cough. Table 2. Lists the target doses of the ARBs in treatment of HF.

Aldosterone Antagonists

Utility of aldosterone antagonists such as Spironolactone, or Eplerenone are limited in

acute HF setting. They are further discussed in the chronic HF section. Aldosterone

antagonists do facilitate the diuretic effect of loop diuretics in a congested HF patient

(22-23).

8

Hydralazine/Nitrates

In HF patients with significant renal dysfunction or uncontrolled hypertension despite

maximum dose of ACE and BB, afterload reducers such as combination of hydralazine

and nitrates can be used. While the benefit of hydralazine and nitrates combination has

been shown mostly in African American population, this combination should be

considered in non African Americans when ACE/ARB are not tolerated, or resistant

hypertension is present (24).

Digoxin

Perhaps one of the oldest medications available, digoxin still has a role in treatment of

HF patient. Digoxin is also the only safe and effective oral inotrope agent that has been

identified so far. While this medication does not affect mortality, it has shown to reduce

hospitalization in HF patient population (25). Digoxin’s ideal use is in HFrEF patients

with concomitant atrial fibrillation. This medication has a narrow therapeutic index and

its serum levels should be kept at 0.5 to 0.9 ng/ml. The dose of this medication should

be reduced in renally impaired patients.

9

Inotropes

10

Inotropic therapy is reserved for severely decompensated HF patient with signs of

shock or hypo perfusion organ injury. Low cardiac output or shock can be obvious such

as low pulse pressure, tachycardia, hypotension, and cool extremities. In some cases

however, signs of low cardiac output can be subtle such as worsening of renal function

with loop diuretics in a congested patient, changes in mental status, or abnormal liver

function tests. Invasive hemodynamic monitoring is usually required to assess and

manage patients with low cardiac output or shock. In this section, we will discuss some

of the commonly used inotropic agents.

Milrinone

Phosphodiesterase (PD) inhibitors block the degradation of cyclic adenosine

monophosphate leading to an increase in calcium influx into the myocardium and

enhance contractility. PD inhibitors also have a vasodilatory effect on the pulmonary

and peripheral circulation. Intravenous milrinone can be considered in HF patients with

low cardiac output. This medication should be initiated at low dose and titrated to

achieve acceptable hemodynamics. Since this class of drugs are also potent

vasodilators, their use should be avoided in severely hypotensive patients. Concomitant

use of low dose beta blockers is possible with this class of medications since they

increase contractility independent of the beta adrenergic pathway (26).

Dobutamine

Beta adrenergic receptor agonists can also provide enhanced contractility and

hemodynamic support in severely decompensated HF patients with low cardiac output.

As compared to PD inhibitors, Dobutamine has a less vasodilatory effect on the

periphery and is the preferred medication in hypotensive patients. Concomitant use of

beta blockers, specially the non-selective class, should be avoided as they counteract

utilizing the same receptor.

In general, use of intravenous inotropes is a temporary measure to provide

hemodynamic support as a bridge to recovery or advance therapies (transplant or Left

ventricular Assist Devices ). Long term use of inotropes should be avoided except as

palliative therapy in stage D HF patients, once all available therapies have been

exhausted (27-28).

Use of agents with both inotropic and vasopressor property such as norepinephrine

should only be used in profoundly hypotensive patients with hemodynamic collapse or

sepsis. Pure vasopressors such as phenylephrine should generally be avoided in HF

patients.

Mechanical Circulatory Support

11

In critically ill HF patients with severe hemodynamic compromise who are not

responsive to medical therapy, Mechanical Circulatory Support (MCS) can be utilized to

provide a bridge to recovery or advanced therapies. Intra-aortic balloon pumps are

commonly used devices to provide support to an unstable HF patient. There are a

number of newer MCS devices available for the end-stage patient. While they all

provide hemodynamic support for unstable HF patients, one should recognize that each

device has its challenges and side effects. These devices should only be utilized in

highly skilled facilities with well trained support staff. Some of the more commonly used

new devices are listed bellow:

• Extracorporeal Membrane Oxygenation (ECMO)

• TandemHeart

• Impella

• Centrimag

Chronic Heart Failure Management

In this section we will discuss management of chronic HF patient in an outpatient

setting. Most of the initial work up of HF patient is usually done on the initial

presentation in a hospital setting. It is important to obtain the comprehensive record of

all the work up of the HF patient and start an individual profile for each patient.

Outpatient management of HF serves as a checkpoint to address etiology,

medication/device optimization, symptoms, advance therapies or palliative care.

Etiology

Management of HF patients in an outpatient setting begins with further narrowing down

the differential diagnosis of HF etiologies. This step will ensure that all the reversible

causes of HF have been investigated and either addressed, or ruled out. Presence of

coronary disease, resistant hypertension, substance abuse, thyroid abnormalities,

arrhythmias, and exposure to toxins are a few common and possibly reversible

etiologies of HF. This information is key in tailoring the outpatient treatment to individual

HF patients and improving outcomes.

Medication Optimization

Management of HF medications is a challenging, yet critical step in the outpatient

setting. In patients with HFrEF, every effort should be made to include beta blockers,

ACE inhibitors and aldosterone antagonists as part of medical therapy of chronic HF.

The doses of these medications should be titrated up as tolerated by patients (Table 2.).

Additional medical therapy such as Hydralazine/Nitrates combination, digoxin, and

diuretics should also be initiated and maintained if HF patient continues to be

12

symptomatic or struggles with volume overload. ARBs should be utilized in HF patients

who are ACE intolerant.

Volume Statue and Symptom Surveillance

Monitoring HF patient’s volume status in an outpatient setting using physical exam

(JVD, weight, edema) labs (BNP, sodium) and devices is crucial in maintaining the

patient’s overall quality of life and avoiding hospitalizations. HF patients should be

advised to monitor their daily weights and report any sudden significant changes (> 2

lbs/day or 5 lb/week) to their HF care provider (29). The diuretic therapy can be

adjusted accordingly.

New York Heart Association (NYHA) functional classification is a simple and robust way

of monitoring patients’ symptoms in an outpatient setting. The clinician’s goal is to get

the HF patient to Class I or II functional class, and escalate the level of care in

functional classes III, and IV.

Device Optimization

Cardiac devices such as Implantable Cardioverter Defibrillator (ICD) or Cardiac

Resynchronization Therapy (CRT) are now widely used in HFrEF patients who meet

criteria. As part of the evaluation of HF patient in an outpatient setting, the clinicians

should address the patient’s candidacy for device therapy. In general, HFrEF patients

with ejection fraction less than 35% who are optimized on medical therapy more than 3-

6 months should be considered for ICD implantation. Patients with EF < 35% due to

acute myocardial infarction should wait for 40 days prior to ICD implantation (30-32).

ICDs should be reserved for patients with a reasonable expectation of survival in one

year, and adequate quality of life.

Patients with HFrEF and wide QRS morphology (ideally left bundle morphology with

QRS >150 ms) should be referred for CRT evaluation. Persistent right ventricular pacing

due to atrioventricular block or atrial fibrillation with slow ventricular response are also

indications for CRT in HFrEF patients.

Referral to Advance Heart Failure Program

Despite optimal medical therapy, revascularization, and device therapies, a certain

percentage of HF patients will progress to more advanced stages of the disease. The

transition of a HF patient from stable on medical therapy, to an advanced stage

requiring mechanical circulatory support (MCS) or heart transplantation can be subtle.

Here are some clinical findings that should trigger a referral to an advanced heart failure

program:

13

-Persistent NYHA class III-IV despite medical/device therapy

-Deteriorating renal or liver function (BUN>40 mg/dL or creatinine >1.8 mg/dL)

-Beta blocker or ACE inhibitor intolerance due to hypotension

-Increasing diuretic requirements (>120 mg/day or equivalent)

-Recurrent hospitalizations for HF (more than 1 in 6 months)

It is imperative to realize that once the patient develops irreversible organ damage,

advanced therapies such as heart transplantation and Left Ventricular Assist Devices

(LVADs) may no longer be options. Therefore, timely referral to heart failure program is

important.

Hospice

As mentioned at the beginning of this chapter there are over 5 million patients who

suffer from heart failure. Approximately, 5% of the HF patient population is classified as

NYHA IV, stage D. A small portion of the NYHA IV patients will receive heart

transplantation or LVAD therapy, however, majority of them will not be candidates for

advanced therapies with very poor outcomes (Figure 2). Patients with end stage HF

have recurrent hospitalizations, deteriorating renal function, and poor quality of life. The

patients and their caregivers are also burdened with significant physical and emotional

stress at the final moths of life (32). Since the trajectory of end stage heart failure is well

known and documented, it is imperative for the physician to recognize and address

such situations. Listed below are some of the signs that should prompt the clinician to

start the end of life discussion with the patient and their family.

-NYHA IV symptoms despite optimal medical, surgical, and device therapies

-Deemed a poor candidate for transplant or LVAD

-Recurrent hospitalizations despite good compliance

-Persistent ventricular arrhythmias despite medical and surgical interventions

-Profound cardiac cachexia

End of life discussions are always difficult, both for the patient and clinicians. The

primary physician’s role is crucial in approaching the end stage patient, as they usually

have a closer and longer bond with the patient and their family. Some of the common

symptoms of end stage HF are dyspnea, fatigue, pain, anorexia and cachexia.

Management of the HF patient in the palliative care and hospice stage focuses on

patient’s comfort and quality of life.

Dyspnea can be treated with continuous infusion of home inotropes. Nitrates, opioids

and home oxygen are also effective in alleviating breathlessness. Caffeine and certain

stimulants have been used to address fatigue in certain HF patients. Titrating down the

14

dosage of beta blockers and ACE inhibitors, or stopping a class of medication

altogether can also be considered in hypotensive patients.

End stage HF patients are prone to tachyarrhythmias and recurrent ICD shocks. ICD

therapy should also be discussed with the patient and the family. While discontinuing

the defibrillating capability of the ICDs is a reasonable approach, the CRT portion of the

devices should be continued as it may provide symptom relief.

15

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